INTRODUCTION — Primary cutaneous B cell lymphoma (PCBCL) refers to those cases of B cell lymphoma that present in the skin when there is no evidence of extracutaneous disease at the time of diagnosis and after the completion of an initial staging evaluation. The most recent World Health Organization (WHO) classification system and the 2018 update of the WHO-European Organization for Research and Treatment of Cancer (EORTC) classification for primary cutaneous lymphomas define three main subtypes of PCBCL that have distinct clinical presentations, pathologic features, prognosis, and treatment [1,2]:
●Primary cutaneous follicle center lymphoma (PCFCL)
●Primary cutaneous large B cell lymphoma, leg type
●Primary cutaneous marginal zone lymphoma (PCMZL). In the 2017 revised WHO classification PCMZL is included in the broader category of extranodal marginal zone B cell lymphoma 
This topic review will discuss PCFCL. This entity was previously known as primary cutaneous follicle center cell lymphoma (PCFCCL) under the European Organization for Research and Treatment of Cancer (EORTC) classification and contains cases that may have previously be classified as cutaneous follicle center lymphoma or diffuse large B cell lymphoma under the 2001 WHO classification.
Our suggestions for management are consistent with those proposed by the International Society for Cutaneous Lymphoma, the International Lymphoma Radiation Oncology Group, and the National Comprehensive Cancer Network (NCCN) [3-6].
The other PCBCL subtypes and other forms of cutaneous lymphoma (ie, T cell lymphoma, mycosis fungoides) are presented separately.
EPIDEMIOLOGY — Approximately 25 percent of all non-Hodgkin lymphoma (NHL) cases will present at an extranodal site without systemic involvement. The skin is the second most common primary extranodal site, second in frequency only to the gastrointestinal tract. The overall incidence of primary cutaneous lymphomas in Western countries is estimated to be 0.5 to 1 case per 100,000 people annually. Of these, approximately 20 to 25 percent represent primary cutaneous B cell lymphoma (PCBCL) [2,7,8]. The incidence varies geographically with lower rates in Japan and Korea [9,10].
PCFCL is the most common PCBCL, accounting for approximately 50 percent of such cases . Although the disease does occur in patients as young as 20 [11,12], it is primarily a disease of middle aged to older patients (median age at onset is 51) and a male:female ratio of approximately 1.5:1 [1,13,14]. The vast majority of cases occur in non-Hispanic White individuals .
PATHOGENESIS — There are no clearly defined risk factors for developing this disease and there is no identifiable hereditary tendency.
B cell receptor genes in PCFCL can acquire N-linked glycosylation motifs; this observation is similar to nodal follicular lymphomas, but contrasts with primary cutaneous diffuse large B cell lymphoma, leg type . These observations may suggest a role for lectins from commensal skin bacteria in the pathogenesis of PCFCL.
Pathogenetic links between primary cutaneous B cell lymphoma (PCBCL) and Borrelia burgdorferi infection have been established in Europe, but North American and Asian case series have thus far failed to demonstrate a similar relationship. B. burgdorferi infection is seen more commonly in primary cutaneous marginal zone lymphoma, and only rarely in PCFCL. Although several case reports have suggested a link between PCBCL and viral infection (eg, Epstein-Barr virus, HIV, and hepatitis C virus), no definitive evidence exists. This is discussed in more detail separately. (See "Primary cutaneous marginal zone lymphoma", section on 'Pathogenesis'.)
CLINICAL FEATURES — PCFCL typically presents with solitary or grouped firm erythematous, painless, nonpruritic papules, plaques, or tumors with a predilection for the head, neck, and trunk (picture 1A-B) [16-18]. Approximately 5 percent of patients have lesions on the legs while 15 percent present with multifocal skin lesions [1,13,16].
The lesions are generally smooth and do not typically ulcerate; superficial scaling may be present [19,20]. Surrounding annular erythema, which may be papular, has been described . Most cases consist of a solitary lesion <5 cm (stage IAE) . Disseminated lesions are rare, although cases with a dermatomal distribution have been reported . A multicenter retrospective study described the presence of small papular skin lesions located at a distance of the main affected area in 3 of 24 patients with a PCFCL . Interestingly, these distant lesions resolved spontaneously in all three patients.
The lesions tend to progress slowly and may be present for more than 20 years before a diagnosis is established; a latent phase of several years is the norm . Systemic "B" symptoms (ie, fever, weight loss, night sweats) were reported in only 2 of 84 cases in one series .
Morphology — Skin biopsy specimens demonstrate dermal and subcutaneous infiltration, which almost always spares the epidermis . The area of infiltration can be perivascular, periadnexal, or diffuse. Growth can be in a follicular, follicular and diffuse, or diffuse pattern. When a follicular pattern is present, the follicles are ill-defined, have a decreased mantle zone, lack tingible body macrophages, and show a monotonous proliferation of BCL6+ follicle center cells. Interfollicular areas contain a mixed cellular population of small and large lymphocytes and histiocytes. In more advanced PCFCL, the follicles may be less pronounced or absent.
The malignant lesions are comprised of predominantly medium-sized and large centrocytes (large cleaved follicle center cells) and variable proportions of centroblasts (large follicle center cells with prominent nucleoli) (picture 2) . In some cases, the centrocytes are intermixed with multilobated cells and spindle cells (picture 3).
Unlike nodal follicular lymphoma, PCFCL is not routinely graded since there is no correlation between grading and prognosis.
Immunophenotype — PCFCL is a B cell malignancy thought to arise from mature germinal center cells. Virtually all cases express pan B cell antigens (CD19, CD20, CD79a) and are always CD5 negative . Most cases express B cell leukemia 6 (BCL-6) and do not express B cell leukemia/lymphoma 2 (BCL-2) . CD10 expression is variable . The plasma cell marker MUM1/IRF4 is negative . Staining for kappa and lambda light chains may reveal monotypic surface immunoglobulin or the cells may lack surface immunoglobulin. Cytoplasmic immunoglobulin is usually negative. Markers of proliferation are variable with one report demonstrating 9 of 24 cases with 60 to 90 percent Ki-67 positive cells . Staining with CD21 or CD35 usually reveals focal remnants of follicular dendritic cell meshwork .
Genetics — There is no single cytogenetic change that is typical or diagnostic. Genotypic studies may be used to document clonality. While the majority of nodal follicular lymphomas have a t(14;18) translocation and/or BCL2 gene rearrangement , the reported incidence of BCL-2 expression and the t(14;18) translocation in PCFCL has ranged from zero [23,31,32] to as high as 30 to 40 percent [12,33].
PCFCL shows the gene expression profile of germinal center-like large B cell lymphomas, and often shows amplifications of the REL gene [29,34]. Deletion of chromosome 14q32.33 has been reported . A subset of PCFCL patients may show 1p36 deletions and/or somatic mutations of the TNFRSF14 gene [35-37]. Mutations in CREBBP and KTM2D are significantly less common in PCFCL than in nodal follicular lymphomas [36,37]. In contrast to primary cutaneous B cell lymphoma, leg type, deletions of a small region on chromosome 9p21.3 containing the CDKN2A and CDKN2B gene loci and MYD88 mutations are not or only rarely found in PCFCL [34,38]. (See "Prognosis of diffuse large B cell lymphoma", section on 'Overview'.)
DIAGNOSIS — The diagnosis of PCFCL is made based upon a pathologic evaluation of a skin biopsy in a patient who has no evidence of systemic lymphoma upon staging studies. The diagnosis of PCFCL requires a representative biopsy of involved skin and the exclusion of non-cutaneous disease. Excisional biopsies are preferred to punch biopsies, but if a punch biopsy is taken, the diameter should be at least 4 mm. (See 'Staging' below.)
The biopsy specimen is evaluated for morphology, growth pattern, and immunohistochemical studies. A typical biopsy of PCFCL demonstrates an epidermis-sparing B cell infiltrate comprised of centrocytes and centroblasts with a follicular or diffuse pattern. B cell lineage is confirmed by the presence of CD20 or CD79a and the absence of CD3.
DIFFERENTIAL DIAGNOSIS — Patients with PCFCL present with solitary or grouped firm, erythematous, painless, nonpruritic papules, plaques, or tumors with a predilection for the scalp, forehead, neck, and trunk that can mimic arthropod bites, cutaneous lymphoid hyperplasia, and other cutaneous lymphomas, all of which can be distinguished by pathologic review of a skin biopsy with morphologic evaluation and immunohistochemical stains (table 1).
This pathologic distinction is based upon three main factors :
●Identifying the infiltrate as clonal (not reactive), often by demonstrating clonal Ig gene rearrangements on paraffin sections or frozen section (or by flow cytometry).
●Determining that the neoplastic cells are of B cell origin (not T cell or NK cell), usually by demonstrating the presence of B cell antigens (eg, CD20) and absence of T cell antigens (eg, CD3). Importantly, while the neoplastic cells are of B cell origin, there can be many admixed reactive T cells in the infiltrate.
●Confirming that the infiltrate has morphologic and immunophenotypic features of PCFCL, rather than another cutaneous B cell lymphoma (primary cutaneous marginal zone lymphoma or primary cutaneous diffuse large B cell lymphoma, leg type), as based upon the morphology and immunophenotype.
●Staging studies are performed to confirm that involvement is limited to the skin. (See 'Staging' below.)
Reactive infiltrate — One of the most important diagnostic considerations in all primary cutaneous B cell lymphoma (PCBCL) subtypes is differentiating a neoplastic B cell infiltrate from a reactive infiltrate. Follicular hyperplasia seen with inflammation (eg, Borrelia burgdorferi infection, tick bites) can mimic PCFCL.
Ki-67 staining can determine the proliferative fraction and aid in the differentiation between neoplastic and reactive follicles. The Ki-67+ fraction is lower in PCFCL with a follicular growth pattern than in reactive follicles, but in PCFCL with a diffuse growth pattern, the proliferative fraction is generally >75 percent. (See "Clinical manifestations, pathologic features, diagnosis, and prognosis of follicular lymphoma", section on 'Reactive follicular hyperplasia'.)
Unlike the follicles seen in cutaneous follicular hyperplasia, the follicles in PCFCL are ill-defined, have a decreased mantle zone, lack tingible body macrophages, and show a monotonous proliferation of BCL-6+ follicle center cells in a network of CD21+ or CD35+ follicular dendritic cells.
Follicular lymphoma — Non-Hodgkin lymphoma (NHL) may involve the skin either as a primary entity or as the result of cutaneous spread from systemic disease. An estimated 6 to 10 percent of patients with systemic B cell NHL will develop cutaneous disease at some point in their illness .
Biopsy specimens from follicular lymphoma (FL) can resemble those of PCFCL by morphology and immunophenotype. Characteristically, the tumor cells of FL express monotypic immunoglobulin (Ig) light chain, CD20, CD10, and BCL-6 and are negative for CD5 and CD23. The vast majority (>85 percent) of FL tumors express BCL-2, and show the t(14;18) rearrangement.
In contrast, PCFCL only rarely expresses immunoglobulin and most cases are BCL-2 negative. CD10 expression is variable. Strong expression of BCL-2, BCL-6, and CD10 should raise the suspicion of systemic follicular lymphoma with skin involvement. (See "Clinical manifestations, pathologic features, diagnosis, and prognosis of follicular lymphoma".)
Intravascular lymphoma — Intravascular large B cell lymphoma is a distinctly uncommon NHL variant that typically presents as multiple, erythematous tender nodules, tumors, or telangiectasias in older patients. Isolated involvement of the skin does occur, but the disease more frequently affects multiple organ systems, including the central nervous system, kidneys, and adrenals producing a wide variety of symptoms, ranging from generalized confusion or dementia to focal motor and sensory deficits. This is discussed in more detail separately. (See "Intravascular large cell lymphoma".)
Other cutaneous lymphomas
Primary cutaneous diffuse large B cell lymphoma, leg type — It is important to differentiate PCFCL from primary cutaneous diffuse large B cell lymphoma, leg type since the latter is far more aggressive and requires a different treatment approach. Despite its name, primary cutaneous diffuse large B cell lymphoma, leg type can occur at sites other than the leg. These lesions have a diffuse pattern or a monotonous proliferation of centroblasts and/or immunoblasts on biopsy, and, in contrast to PCFCL, strongly express BCL-2, MUM1, FOXP1 and IgM. A subset of patients with primary cutaneous diffuse large B cell lymphoma, leg type will have mutations in MYD88 ; MYD88 mutations are not seen in PCFCL. (See "Primary cutaneous large B cell lymphoma, leg type".)
Primary cutaneous marginal zone lymphoma — PCFCL can be differentiated from primary cutaneous marginal zone lymphoma (PCMZL) based upon differences in clinical presentation and pathologic findings on the skin biopsy. PCFCL is characterized by a diffuse infiltrate of large cleaved cells (large centrocytes) with a BCL-6+, BCL-2-, CD10-/+ phenotype. In contrast, the neoplastic cells of PCMZL have a BCL-6-, BCL-2+, CD10- phenotype. Moreover, monotypic cytoplasmic Ig light chain expression by the lymphoplasmacytoid and plasma cells (typically located at the periphery of the nodular infiltrates and subepidermally) is a hallmark of PCMZL and rarely observed in PCFCL. Morphologically, differentiation between PCFCL with a (partly) follicular growth pattern and PCMZL with reactive follicular structures may sometimes be difficult. However, in such cases, the differential expression of BCL-6, BCL-2 and CD10 may result in the correct diagnosis. It should be noted that colonization of follicular structures by neoplastic marginal zone cells, as often observed in extranodal marginal zone lymphomas arising at other sites, is rarely seen in PCMZL. (See "Primary cutaneous marginal zone lymphoma".)
Cutaneous T cell lymphoma — Cutaneous T cell lymphomas can be distinguished from cutaneous B cell lymphomas through their expression of T cell markers such as CD2, CD3, and CD5. In addition, cutaneous T cell lymphomas can be identified by T cell receptor (TCR) gene rearrangement studies. This is discussed in more detail separately. (See "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides", section on 'Diagnosis'.)
STAGING — At the time of diagnosis, patients with suspected primary cutaneous lymphoma should undergo a complete history, physical examination, and staging evaluation. This evaluation both confirms the diagnosis of primary cutaneous lymphoma by excluding involvement of other sites and provides information to guide treatment. We perform the following studies as part of this staging evaluation:
●Laboratory studies include a complete blood count, comprehensive serum chemistries, and serum lactate dehydrogenase (LDH). Flow cytometry of the peripheral blood mononuclear cells is indicated for patients with a lymphocytosis. In addition, all patients with newly diagnosed lymphoma should undergo HIV testing.
●Radiographic imaging with a contrast-enhanced computed tomography (CT) scan of the chest, abdomen and pelvis or combined positron emission tomography (PET)/CT scan should be performed. The neck should be included in case of head and neck lesions and if there is palpable adenopathy. Magnetic resonance imaging (MRI) is often substituted for patients who are unable to safely undergo CT scan. Suspicious lesions should be biopsied.
●Unilateral bone marrow aspiration and biopsy. We usually perform a bone marrow evaluation for patients with cytopenias and for all patients prior to the initiation of therapy. This is principally because a bone marrow biopsy demonstrating involvement would lead the clinician to offer systemic therapy rather than skin directed therapy such as radiation.
If any of the above demonstrates disease outside of the skin in a newly diagnosed patient, strong consideration should be given to the diagnosis of systemic lymphoma. The presence of "B" symptoms, abnormal blood counts, elevated beta-2-microglobulin, or an elevated LDH should also raise suspicion of a systemic lymphoma. (See "Pretreatment evaluation and staging of non-Hodgkin lymphomas".)
Using information gathered from the above tests, patients are staged using the EORTC/International Society for Cutaneous Lymphomas (ISCL) TNM (tumor, node, metastases) staging system for primary cutaneous lymphomas other than mycosis fungoides and the Sézary syndrome (table 2) .
TREATMENT — PCFCL is a rare disorder; accordingly, large trials and a consensus regarding therapy are lacking. The published data regarding treatment consist entirely of retrospective reviews and anecdotal reports. The generally indolent nature of PCFCL has shifted focus to localized, low morbidity modalities such as radiotherapy.
If left untreated, the lesions typically increase in size gradually over years and only disseminate to extracutaneous sites in approximately 10 percent of patients [13,16,18]. Our treatment approach depends upon the number of lesions, their location, and the presence of symptoms attributable to the lesions:
●For patients with a solitary lesion or lesions that can be contained in one radiation field, we suggest treatment with radiation therapy rather than chemotherapy or surgical excision . The International Lymphoma Radiation Oncology Group (ILROG) and the National Comprehensive Cancer Network (NCCN) recommend a dose of 24 to 30 Gy to a field that includes a margin of at least 1 to 1.5 cm of uninvolved skin [4,6]. Alternatively, small solitary lesions may be excised surgically or patients may be observed.
Our preference for the use of radiation therapy is largely because almost all patients treated with radiation therapy obtain a complete response with low toxicity and a low relapse rate when administered with appropriate margins of normal appearing tissue. Radiation toxicity varies by site and cases that require radiation to fields that have high rates of complications may benefit from a lower dose of radiation, alternative therapy, or observation.
●For patients with a few scattered lesions not able to fit in one radiation field, we suggest treatment with either radiation therapy to all visible lesions or initial observation rather than excision or multiagent chemotherapy. If initial observation is chosen, radiation treatment can be administered to symptomatic skin lesions as they develop. In such cases, low-dose radiotherapy (2x2 Gy) often suffices .
●For patients with extensive, diffuse disease, we suggest treatment with single agent rituximab rather than observation, radiation therapy, or multiagent chemotherapy. This approach aims to limit exposure to potentially toxic systemic agents given the indolent nature of these tumors. We reserve combination chemotherapy for the rare case with extremely extensive, symptomatic disease or those who fail to respond to initial rituximab.
With this approach, systemic spread and disease-related deaths are uncommon, occurring in roughly 10 and 5 percent of patients, respectively, over a 10-year period [23,42,43].
Support for this approach comes from retrospective studies and case reports. The largest literature review included data from 713 patients with PCFCL and reported the following outcomes by treatment modality :
●Radiation therapy – Compilation of data on 460 patients treated with 20 to 54 Gy of radiation revealed a 99 percent complete response rate. The relapse rate varied from 30 to 76 percent in the largest studies . This variance may reflect differences in radiation technique. Studies that included a smaller margin of healthy appearing skin in the radiation field reported in-field and marginal recurrences that were not found in studies that used larger margins . One study demonstrated responses to lower doses (4 Gy in two fractions) of radiation .
●Surgical excision – Of 93 patients treated with complete surgical excision 98 percent obtained a complete response, but skin relapse was seen in approximately 40 percent .
●Rituximab – A small number of patients treated with intralesional or systemic rituximab have been reported with complete response rates of 80 to 90 percent [3,44-46]. Relapses in the skin are seen in the majority of patients with a median duration of response of approximately 40 months . A trial of intralesional rituximab in 35 patients with PCFCL or PCMZL reported a complete response (CR) in 71 percent with a median time to CR of eight weeks . Median disease-free survival was approximately two years.
●Multiagent chemotherapy – Cumulative data on 104 patients treated with multiagent chemotherapy, mostly CHOP-like, demonstrated complete responses in 85 percent . Most patients presented with large tumor burdens and relapses were seen in 48 percent. There are even fewer reports of R-CHOP in this disease with mixed results.
●Combined modality therapy – There have also been a few reports of multiagent chemotherapy followed by involved field radiation therapy as used in diffuse large B cell lymphoma. Cumulative data on seven patients reported complete responses in all with one developing relapse .
●Other agents – Case reports have described clinical responses to intralesional interferon alfa, topical class 1 corticosteroids (eg, clobetasol), topical nitrogen mustard, intralesional steroids, and cryotherapy .
FOLLOW-UP — Following the completion of therapy, patients are seen at periodic intervals to monitor for treatment complications and assess for possible relapse. The frequency and extent of these visits depends upon the comfort of both the patient and physician. When planning the post-treatment surveillance strategy, care should be taken to limit the number of radiologic scans, particularly in younger individuals, given concerns about radiation exposure and the risk for second malignancies. (See "Radiation-related risks of imaging".)
For patients who are in complete remission, we typically re-evaluate with a physical examination every three months for the first two years following therapy. The frequency of clinic visits is then decreased thereafter. We do not use imaging studies or blood examinations in the routine follow-up of asymptomatic individuals. This is principally because recurrences are almost always detected by clinical examination. In a retrospective analysis that included 20 patients with PCFCL followed for a median of 66 months, there were 23 episodes of recurrence, all of which were identified by physical examination . Neither blood examinations nor imaging procedures established recurrence or progression in any patient.
TREATMENT AT RELAPSE — Approximately 30 percent of patients initially treated with radiation therapy will relapse. Most relapses are confined to the skin. If they appear outside of the prior radiation field, most will respond to radiation therapy. If they occur inside the radiation field, surgical excision or single agent rituximab may be used. While multiagent chemotherapy remains an option for difficult to treat disease, it is rarely necessary. (See 'Treatment' above.)
The rare patient who develops extracutaneous disease may be managed as systemic follicular lymphoma. This is discussed in more detail separately. (See "Initial treatment of stage II to IV follicular lymphoma".)
PROGNOSIS — Patients with PCFCL usually have an indolent clinical course. If left untreated, the lesions typically increase in size gradually over years. Dissemination to extracutaneous sites is uncommon. In two studies, 18 of 171 (10 percent) and 26 of 243 (10.7 percent) patients developed extracutaneous disease [13,16]. Retrospective analyses suggest that following initial treatment with radiation therapy, up to 30 percent of patients will relapse [3,18]. PCFCL have an excellent prognosis with reported five-year survival rates of approximately 95 percent [7,12,13,16,31,42,49]. Growth pattern (follicular, follicular and diffuse, or diffuse), number of blast cells, the extent of skin lesions (solitary, regional, or multifocal), the presence or absence of t(14;18), or BCL-2 expression have no significant effect on survival. However, PCFCL presenting with skin lesions on the leg are reported to have a more unfavorable prognosis [16,50,51].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary cutaneous lymphoma".)
SUMMARY AND RECOMMENDATIONS
●Primary cutaneous B cell lymphoma (PCBCL) refers to those cases of B cell lymphoma that present in the skin when there is no evidence of extracutaneous disease at the time of diagnosis and after the completion of an initial staging evaluation. Primary cutaneous follicle center lymphoma (PCFCL) is the most common PCBCL. (See 'Introduction' above and 'Epidemiology' above.)
●Patients typically present with firm, erythematous, painless, nonpruritic papules, nodules or plaques with a predilection for the head, neck, and trunk. The lesions are generally smooth and do not typically ulcerate. Disseminated lesions are rare. (See 'Clinical features' above.)
●The diagnosis of PCFCL requires a representative biopsy of involved skin and the exclusion of non-cutaneous disease in the appropriate clinical setting. A typical biopsy of PCFCL demonstrates an epidermis-sparing B cell infiltrate comprised of centrocytes and centroblasts with a follicular or diffuse pattern. B cell lineage is confirmed by the presence of CD20 or CD79a and the absence of CD3. (See 'Pathologic features' above and 'Diagnosis' above and 'Differential diagnosis' above.)
●The staging evaluation both confirms the diagnosis by excluding involvement of other sites and provides information to guide treatment. (See 'Staging' above.)
●PCFCL is a rare disorder; accordingly, large trials are lacking. Published data regarding treatment consist entirely of retrospective reviews and anecdotal reports. In general, our treatment approach depends upon the number of lesions, their location, and the presence of symptoms attributable to the lesions:
•For patients with focal disease (a solitary lesion or lesions that can be contained in one radiation field), we suggest treatment with radiation therapy, rather than chemotherapy, surgical excision, or observation (Grade 2C). A dose of 24 to 30 Gy of radiation should be delivered to a field that includes a margin of at least 1 to 1.5 cm of uninvolved skin. Surgical excision or observation is an acceptable alternative for lesions that are not amenable to radiation therapy (eg, in a location at which radiation toxicity is increased). The choice between these two alternatives depends upon the morbidity associated with excision. (See 'Treatment' above.)
•For patients with a few scattered lesions not able to fit in one radiation field, we suggest treatment with either low-dose radiation therapy to all visible lesions or initial observation rather than excision or multiagent chemotherapy (Grade 2C). The choice to irradiate or not depends upon the sites involved and expected toxicity of radiation to the area and the presence or absence of symptoms. (See 'Treatment' above.)
•For patients with extensive, diffuse disease, we suggest treatment with single agent rituximab rather than observation, radiation therapy, or multiagent chemotherapy (Grade 2C). We reserve combination chemotherapy for the rare case with extremely extensive, symptomatic disease or those who fail to respond to initial rituximab. (See 'Treatment' above.)
●Approximately 30 percent of patients initially treated with radiation therapy will relapse. Most relapses are confined to the skin and are treated with the same modalities as initial therapy. (See 'Treatment at relapse' above.)
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